"Rescue Me!" centers around Masaru, a high school student who finds himself in an unusual predicament when he is saved from a dangerous situation by a mysterious girl named Mashiro. Mashiro reveals herself to be a supernatural entity known as a "Spirit," tasked with protecting humans from malevolent spirits called "Phantoms." However, Mashiro’s presence complicates Masaru’s life, as her powers are tied to his emotional state. The more Masaru feels affection or attraction toward her, the stronger her abilities become, but this also puts him at greater risk of being targeted by Phantoms.

The narrative explores the evolving dynamic between Masaru and Mashiro as they navigate their unusual partnership. Masaru, initially reluctant and overwhelmed, gradually accepts his role in supporting Mashiro’s mission. Alongside them are other characters, including Masaru’s childhood friend, Aoi, who becomes entangled in the supernatural conflicts, and additional Spirits who assist in combating the growing threat of Phantoms. The series balances action, humor, and moments of emotional tension as the characters confront both external dangers and their own personal struggles.

The plot delves into the origins of Spirits and Phantoms, revealing a deeper connection between the two entities and the human world. As Masaru and Mashiro grow closer, their bond becomes a focal point for both their strength and vulnerability. The series culminates in a climactic confrontation with a powerful Phantom, testing their resolve and the limits of their partnership. Throughout, "Rescue Me!" maintains a focus on themes of trust, sacrifice, and the complexities of human emotions, all while delivering a mix of supernatural battles and character-driven storytelling.